title: Oral apixaban for the treatment of acute venous thromboembolism.
abstract: BACKGROUND
  Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism.
  
  
  METHODS
  In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding.
  
  
  RESULTS
  The primary efficacy outcome occurred in 59 of 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; difference in risk [apixaban minus conventional therapy], -0.4 percentage points; 95% CI, -1.3 to 0.4). Apixaban was noninferior to conventional therapy (P<0.001) for predefined upper limits of the 95% confidence intervals for both relative risk (<1.80) and difference in risk (<3.5 percentage points). Major bleeding occurred in 0.6% of patients who received apixaban and in 1.8% of those who received conventional therapy (relative risk, 0.31; 95% CI, 0.17 to 0.55; P<0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (relative risk, 0.44; 95% CI, 0.36 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups.
  
  
  CONCLUSIONS
  A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding (Funded by Pfizer and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00643201).
authors.affiliation: Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy. agnellig@unipg.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Harry R
authors.initials: HR
authors.lastname: Buller
authors.forename: Alexander
authors.initials: A
authors.lastname: Cohen
authors.forename: Madelyn
authors.initials: M
authors.lastname: Curto
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Gallus
authors.forename: Margot
authors.initials: M
authors.lastname: Johnson
authors.forename: Urszula
authors.initials: U
authors.lastname: Masiukiewicz
authors.forename: Raphael
authors.initials: R
authors.lastname: Pak
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Gary E
authors.initials: GE
authors.lastname: Raskob
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin